Search results for: pulmonary tuberculosis

Authors: Fasil Wagnew, Kerri Viney, Kefyalew Addis Alene, Matthew Kelly, Darren Gray

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Background: Undernutrition is a risk factor for tuberculosis (TB), including poor treatment outcomes. However, evidence regarding the effect of undernutrition on TB treatment outcomes is not well understood. We aimed to evaluate the effect of undernutrition on sputum culture conversion and treatment outcomes among people with multi-drug resistance (MDR)-TB. Methods: We searched for publications in the Medline, Embase, Scopus, and Web of Science databases without restrictions on geography or year of publication. We conducted a random-effect meta-analysis to estimate the effects of undernutrition on sputum culture conversion and treatment outcomes. Two reviewers independently assessed the study eligibility, extracted the necessary information, and assessed the risk of bias. Depending on the nature of the data, odds ratio (OR) and hazard ratio (HR) with 95% confidence intervals (CIs) were used to summarize the effect estimates. Potential publication bias was checked using funnel plots and Egger’s tests. Results: Of 2358 records screened, 59 studies comprising a total of 31,254 people with MDR-TB were included. Undernutrition was significantly associated with a lower sputum culture conversion rate (HR 0·7, 95% CI 0·6–0·9, I2=67·1%) and a higher rate of mortality (OR 2·9, 95%CI 2·1–3·8, I2=23·7%) and unfavourable treatment outcomes (OR 1·8, 95%CI 1·5–2·0, I2=72·7%). There was no statistically significant publication bias in the included studies. Three studies were low, forty-two studies were moderate, and fourteen studies were high quality. Interpretations: Undernutrition was significantly associated with unfavourable treatment outcomes, including mortality and lower sputum culture conversion among people with MDR-TB. These findings have implications for supporting targeted nutritional interventions alongside standardised second-line TB drugs.

Keywords: undernutrition, MDR-TB, sputum culture conversion, treatment outcomes, meta-analysis

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Authors: Pegah Ebrahimi, Farshad Oveissi, Iman Manavi-Tehrani, Sina Naficy, David F. Fletcher, Fariba Dehghani, David S. Winlaw

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Despite advances in modern surgery, congenital heart disease remains a medical challenge and a major cause of infant mortality. Cardiovascular prostheses are routinely used in surgical procedures to address congenital malformations, for example establishing a pathway from the right ventricle to the pulmonary arteries in pulmonary valvar atresia. Current off-the-shelf options including human and adult products have limited biocompatibility and durability, and their fixed size necessitates multiple subsequent operations to upsize the conduit to match with patients’ growth over their lifetime. Non-physiological blood flow is another major problem, reducing the longevity of these prostheses. These limitations call for better designs that take into account the hemodynamical and anatomical characteristics of different patients. We have integrated tissue engineering techniques with modern medical imaging and image processing tools along with mathematical modeling to optimize the design of cardiovascular grafts in a patient-specific manner. Computational Fluid Dynamics (CFD) analysis is done according to models constructed from each individual patient’s data. This allows for improved geometrical design and achieving better hemodynamic performance. Tissue engineering strives to provide a material that grows with the patient and mimic the durability and elasticity of the native tissue. Simulations also give insight on the performance of the tissues produced in our lab and reduce the need for costly and time-consuming methods of evaluation of the grafts. We are also developing a methodology for the fabrication of the optimized designs.

Keywords: computational fluid dynamics, cardiovascular grafts, design optimization, tissue engineering

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Authors: Shyan-Lung Lin, Cheng-Yi Huang, Tung-Yi Lin

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Physical fitness is the adaptability of the body to physical work and the environment, and is generally known to include cardiopulmonary-fitness, muscular-fitness, body flexibility, and body composition. This paper is aimed to study the ventilatory and cardiovascular activity under various exercise intensities for subjects at distinct ends of cardiopulmonary fitness norm. Three graded upright biking exercises, light, moderate, and vigorous exercise, were designed for subjects at distinct ends of cardiopulmonary fitness norm from their physical education classes. The participants in the experiments were 9, 9, and 11 subjects in the top 20%, middle 20%, and bottom 20%, respectively, among all freshmen of the Feng Chia University in the academic year of 2015. All participants were requested to perform 5 minutes of upright biking exercise to attain 50%, 65%, and 85% of their maximum heart rate (HRmax) during the light, moderate, and vigorous exercise experiment, respectively, and 5 minutes of recovery following each graded exercise. The cardiovascular and ventilatory signals, including breathing frequency (f), tidal volume (VT), heart rate (HR), mean arterial pressure (MAP), and ECG signals were recorded during rest, exercise, and recovery periods. The physiological signals of three groups were analyzed based on their recovery, recovery rate, and percentage variation from rest. Selected time domain parameters, SDNN and RMSSD, were computed and spectral analysis was performed to study the hear rate variability from collected ECG signals. The comparison studies were performed to examine the correlations between physical fitness norm and cardio-pulmonary signals during graded exercises and exercise recovery. No significant difference was found among three groups with VT during all levels of exercise intensity and recovery. The top 20% group was found to have better performance in heart recovery (HRR), frequency recovery rate (fRR) and percentage variation from rest (Δf) during the recovery period of vigorous exercise. The top 20% group was also found to achieve lower mean arterial pressure MAP only at rest but showed no significant difference during graded exercises and recovery periods. In time-domain analysis of HRV, the top 20% group again seemed to have better recovery rate and less variation in terms of SDNN during recovery period of light and vigorous exercises. Most assessed frequency domain parameters changed significantly during the experiment (p<0.05, ANOVA). The analysis showed that the top 20% group, in comparison with middle and bottom 20% groups, appeared to have significantly higher TP, LF, HF, and nHF index, while the bottom 20% group showed higher nLF and LF/HF index during rest, three graded levels of exercises, and their recovery periods.

Keywords: physical fitness, cardio-pulmonary signals, graded exercise, exercise recovery

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Authors: Eli Maria Pazzianotto-Forti, Patrícia Brigatto, Letícia Baltieri, Carolina Moraes Da Costa, Maura Rigoldi Simoes Da Rocha, Irineu Rasera Jr

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The application of positive pressure in airway can contribute to the restoration of lung volumes, capacities and prevent respiratory complications. The aim was to investigate the use of Bilevel Positive Airway Pressure (BIPAP) in morbidly obese in two moments in postoperative bariatric surgery: In the post-anesthetic recovery (PAR) and on the 1st postoperative day (1stPO). Twenty morbidly obese, aged between 25 and 55 years, underwent pulmonary function test and chest X-ray preoperatively and on the day of discharge (2nd day after surgery). They were randomly allocated in groups. GPAR: received BIPAP treatment in PAR, for an hour and G1stPO: received BIPAP for one hour, on the 1stPO. There were significant reductions in slow vital capacity (SVC) (p=0.0007), inspiratory reserve volume (IRV) (p=0.0016) and forced vital capacity (FVC) (p=0.0013) in the postoperative in GPAR and the expiratory reserve volume (ERV) remained (p=0.4446). In the G1stPO, there were significant reductions for: SVC p=<0.0001, ERV p=0.0191, IRV p= 0.0026 and FVC p=<0.0001. Comparing between groups, the SVC (p=0.0027) and FVC (p=0.0028) showed significant difference between the treatments. However, the GPAR showed fewer declines of these capacities. To the ERV (p= 0.1646) and IRV (p=0.3973) there was no significant difference between groups. The atelectasis prevalence was 10% for the GPAR and 30% for G1stPO, with significant difference between the proportions (p = 0.0027). The lowest reduction in SVC and FVC happens when positive pressure is applied in PAR. Thus, the use of BIPAP in the PAR can promote a restoration of ERV and contribute to the reduction of atelectasis. FAPESP 2013/06334-8.

Keywords: atelectasis, bariatric surgery, physiotherapy, pulmonary function, positive pressure

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Authors: Fathia Ehmouda Zaid, Reim Abudelnbi

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Cardiovascular disease is a major cause of morbidity and mortality in patients with systemic lupus erythematosus (SLE). Patients and method: Cross-section study (68) patients diagnosed as systemic lupus erythematosus (SLE), who visited the outpatient clinic of rheumatology, these patients were interviewed with a structured questionnaire about their past and current clinically for presence of Cardiovascular disease in systemic lupus and use SLEDAI, specific tests [ECG –ECHO –CXRAY] the data are analyzed statistically by Pearson's correlation coefficient was calculated and statistical significance was defined as P< 0.05,during period (2013-2014). Objective: Estimation Cardiovascular disease manifestation of systemic lupus erythematosus, correlation with disease activity, morbidity, and mortality. Result: (68) Patients diagnosed as systemic lupus erythematosus' age range from (18-48 years), M=(13±29Y), Sex were female 66/68 (97.1%), male 2/68 (2.9%),duration of disease range[1-15year], M =[7±8y], we found Cardiovascular disease manifestation of systemic lupus erythematosus 32/68 (47.1%), correlation with disease activity use SLEDAI,(r= 476** p=0.000),Morbidity,(r= .554**; p=0.000) and mortality (r=.181; p=.139), Cardiovascular disease manifestations of systemic lupus erythematosus are pericarditis 8/68 (11.8%), pericardial effusion 6/68 (8.8%), myocarditis 4/68 (5.9 %), valvular lesions (endocarditis) 1/68 (1.5%), pulmonary hypertension (PAH) 12/68 (17.6%), coronary artery disease 1/68 (1.5%), none of patients have conduction abnormalities involvement. Correlation with disease activity use SLEDAI, pericarditis (r= .210, p=.086), pericardial effusion (r= 0.079, p=.520), myocarditis (r= 272*, p=.027), valvular lesions (endocarditis) (r= .112, p= .362), pulmonary hypertension (PAH) (r= .257*, p=.035) and coronary artery disease (r=.075, p=.544) correlation between cardiovascular disease manifestations of systemic lupus erythematosus and specific organ involvement we found Mucocutaneous (r=.091 p= .459), musculoskeletal (MSK) (r=.110 p=.373), Renal disease (r=.278*, p=.022), neurologic disease (r=.085, p=.489) and Hematologic disease (r=-.264*, p=.030). Conclusion: Cardiovascular manifestation is more frequent symptoms with systemic lupus erythematosus (SLE) is 47 % correlation with disease activity and morbidity but not with mortality. Recommendations: Focus research to evaluation and an adequate assessment of cardiovascular complications on the morbidity and mortality of the patients with SLE are still required.

Keywords: cardiovascular disease, systemic lupus erythematosus, disease activity, mortality

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Authors: Sutinon Yuchomsuk, Satchachon Changthom, Pruet Areesawangvong, Monsiri Jinapen

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Background: Esophageal squamous cell carcinoma can be presented with many symptoms, such as dysphagia or weight loss. However, in some circumstances, rare presentations can be found, e.g., dyspnea, which is more common in pulmonary malignancy. And dyspnea is also one of the most common presentations of COVID-19 infection. So, in this case, we can learn from many points in patient symptoms and findings leading to the diagnosis of esophageal squamous cell carcinoma. Method: This research is a case-report study including one patient from Mahasarakham Hospital, Thailand. Data were collected during December 2021. Result: A 55-year-old Thai male patient with an unknown past medical history presented with dyspnea and shortness of breath for the duration of three days prior to admission. His symptom also included cough, fever, and sore throat. Laboratory results indicated that the patient had COVID-19 pneumonia. Further investigation showed that he had cardiac tamponade and suspected pulmonary/esophageal cancer. Lung biopsy and pericardiocentesis were done, which were positive for carcinoma from pericardial effusion but negative for malignancy from the lung biopsy. Later esophagogastroduodenoscopy was done with endoscopic tissue biopsy; the result was positive for squamous cell carcinoma of the esophagus. Conclusion: Most commonly, esophageal cancer is presented with dysphagia or weight loss. However, in some rare cases, patients can also be presented with dyspnea due to cardiac tamponade. And in recent years, COVID-19 has become a pandemic all over the world, sometimes masking symptoms of other diseases. Such as in this case, the patient didn’t improve after the pneumonia was resolved, which led to the final diagnosis of metastatic esophageal cancer.

Keywords: esophageal cancer, cardiac tamponade, metastatic squamous cell carcinoma, COVID-19 infection

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Authors: Ibrahim Umar, S Chindo, A Rajab

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Background: TB remains a disease of public health concern in Nigeria with an estimated incidence rate of 219/100,000. Kano has the second highest TB burden in Nigeria and is the leading state with the highest consistent yearly TB notification. House-to-house (H2H) active case search in the community was found to have major contribution to the total TB notification in the state. Aims and Objective: To showcase the impact of H2H community active TB case search (ACF) to yearly TB notification in Kano State, Northern Nigeria from 2012 to 2022. Methodology: This is a retrospective descriptive study based on the analysis of data collected during the routine quarterly and yearly TB data collected in the state. Data was analyzed using the Power BI with statistical alpha level of significance <0.05. Results: Between 2012 and 2013 there was no House-to-house active TB case search in Nigeria and Kano had zero contribution to TB notification from the community in those years. However, in 2014 with the introduction of H2H Active TB Case Search Kano notified 6,014 TB cases out of which 113 came from the community ACF that translated to 2% contribution to total TB notification. From 2014 to 2022 there was progressive increase in community contribution to TB case notification from 113 out of 6,014 total TB patients notified (2012) to 11,799 out of 26,371 TB patients notified (2022) in Kano State. This translated to 45% increase in community contribution to total TB case notification. Discussion: Remarkable increase in community contribution to total TB case notification in Kano State was achieved in 2022 with 11,799 TB cases notified from the community Active TB case search to the total of 26,731 TB cases notified in Kano State, Nigeria. Conclusion: in research has shown that Community-based H2H Active TB Case Search through Community TB Workers (CTWs) is an excellent strategy in finding the missing TB cases towards Ending TB in the world.

Keywords: tuberculosis(TB), active case search (ACF), house-to-house (H2H), community TB workers (CTWs)

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Authors: Ndarusanze Berchmans

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This research work focused on the analysis of the observations of tuberculous meningitis in HIV-positive patients who were treated by the Prince Regent Charles Hospital in Bujumbura. A number of 246 seropositive patients were examined by the laboratory of Prince Regent Charles in the period between 2010 and 2015. We did a retrospective study; we used data from the registers of the laboratories mentioned above; the objective was to approach the epidemiological, biological, clinical, and therapeutic characteristics of tuberculosis meningitis infection: 124 women (50.40% of AIDS patients) and 122 men (49.59% of AIDS patients) were subject to the diagnosis by identification of cerebrospinal fluid (CSF). The average age of the patients was 30 years for this period. The population at risk has an average age of between 34 and 42 years for the years between 2010-2015. From 2010 to 2012, cases of opportunistic diseases (e.g., tuberculous meningitis and Cryptococcus neoformans meningitis), often found in immunocompromised, were observed at a high rate; in this period, there was a disturbance of the rhythm providing antiretroviral drugs to people with AIDS. The rate of the two meningitis (tuberculous meningitis and Cryptococcus neoformans meningitis) remained above 10% to gradually decrease until 2015, with the gradual return of antiretrovirals. This period records an overall average of 25 cases of tuberculous meningitis, or a percentage of 10.16%. For the year 2015, there were 4 cases of tuberculous meningitis out of a total of 35 seropositive examined (11.42%). This year's percentage shows that the number of tuberculous meningitis cases has fallen from the rate in previous years. This is the result of the care given by associations against HIV/AIDS to HIV-positive people. This decrease in cases of tuberculous meningitis is due to the acquisition of antiretrovirals by all HIV-positive people treated by hospitals. For the moment, these hospitals are taking care of many AIDS patients by providing them permanently with antiretrovirals; Besides that, there are many patients who are supported by associations whose activities are directed against HIV/AIDS.

Keywords: Cryptococcus neoformans meningitis, tuberculosis meningitis, neurological complications, epidemiology of meningitis

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Authors: Enjie Xu, Zhen Huang, Kunpeng Zhu, Jianping Hu, Xiaolong Ma, Yongjie Wang, Jiazhuang Zhu, Chunlin Zhang

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Abstract: Hypoxia and dedifferentiation of osteosarcoma (OS) cells leads to poor prognosis. We plan to identify the role of hypoxia on dedifferentiation and the associated signaling pathways. We performed a sphere formation assay and determined spheroid cells as dedifferentiated cells by detecting stem cell-like markers. RNAi assay was used to explore the expression relationship between hypoxia inducible factor 1 subunit alpha (HIF1A) and platelet derived growth factor receptor beta (PDGFRB). We obtained PDGFRB knockdown and overexpression cells through lentiviral infection experiments and the effects of PDGFRB on cytoskeleton rearrangement and cell adhesion were explored by immunocytochemistry. Wound-healing experiments, transwell assays, and animal trials were employed to investigate the effect of PDGFRB on OS metastasis. Dedifferentiated OS cells were found to exhibit high expression of HIF1A and PDGFRB, and HIF1A promoted the expression of PDGFRB, subsequently activated ras homolog family member A (RhoA), and increased the phosphorylation of myosin light chain (MLC). PDGFRB also enhanced the phosphorylation of focal adhesion kinase (FAK). The OS cell morphology and vinculin distribution were altered by PDGFRB. PDGFRB also promoted cell dedifferentiation and had a significant impact on the metastasis of OS cells both in vitro and in vivo. Our results demonstrated that HIF1A up-regulated PDGFRB under hypoxic conditions, and PDGFRB regulated the actin cytoskeleton by activating RhoA and subsequently phosphorylating MLC, thereby promoting OS dedifferentiation and pulmonary metastasis.

Keywords: osteosarcoma, dedifferentiation, metastasis, cytoskeleton rearrangement, PDGFRB, hypoxia

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Authors: Prabir Patel, Eugene Ming Han Lim

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Introduction: Current literature shows that postoperative pulmonary complications following abdominal surgery may be reduced by using lower than conventional tidal volumes intraoperatively together with moderate levels of positive end expiratory pressure (PEEP). The recent studies demonstrated significant reduction demonstrated significant reduction in major complications in elective abdominal surgery through the use of lower tidal volumes (6-8 ml/kg predicted body weight), PEEP of 5 cmH20 and recruitment manoeuvres compared to higher ‘conventional’ volumes (10-12 mls/kg PBW) without lung recruitment. Our objective was to retrospectively audit current practice for patients undergoing major abdominal surgery in Sir Charles Gairdner Hospital. Methods: Patients over 18 undergoing elective general surgery lasting more than 3 hours and intubated during the duration of procedure were included in this audit. Data was collected over a 6 month period. Patients who had hepatic surgery, procedures necessitating one-lung ventilation, transplant surgery, documented history of pulmonary or intracranial hypertension were excluded. Results: 58 suitable patients were identified and notes were available for 54 patients. Key findings: Average peak airway pressure was 21cmH20 (+4), average peak airway pressure was less than 30 cmH20 in all patients, and less than 25 cmH20 in 80% of the cases. PEEP was used in 81% of the cases. Where PEEP was used, 75% used PEEP more than or equal to 5 cmH20. Average tidal volume per actual body weight was 7.1 ml/kg (+1.6). Average tidal volume per predicted body weight (PBW) was 8.8 ml/kg (+1.5). Average tidal volume was less than 10 ml/kg PBW in 90% of cases; 6-8 ml/kg PBW in 40% of the cases. There was no recorded use of recruitment manoeuvres in any cases. Conclusions: In the vast majority of patients undergoing prolonged abdominal surgery, a lung protective strategy using moderate levels of PEEP, peak airway pressures of less than 30 cmH20 and tidal volumes of less than 10 cmH20/kg PBW was utilised. A recent randomised control trial demonstrated benefit from utilising even lower volumes (6-8 mls/kg) based on findings in critical care patients, but this was compared to volumes of 10-12 ml/kg. Volumes of 6-8 ml/kg PBW were utilised in 40% of cases in this audit. Although theoretically beneficial, clinical benefit of lower volumes than what is currently practiced in this institution remains to be seen. The incidence of pulmonary complications was much lower than in the other cited studies and a larger data set would be required to investigate any benefit from lower tidal volume ventilation. The volumes used are comparable to results from published local and international data but PEEP utilisation was higher in this audit. Strategies that may potentially be implemented to ensure and maintain best practice include pre-operative recording of predicted body weight, adjustment of default ventilator settings and education/updates of current evidence.

Keywords: anaesthesia, intraoperative ventilation, PEEP, tidal volume

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Authors: Aastha Agarwal, Veena Sharma

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N-nitrosopyrollidine or NPYR is a tobacco-specific nitrosamine which upon intoxicated causes abnormal production of Reactive Oxygen Species disrupt the endogenous antioxidant system. The study was designed to evaluate the histological changes in lung tissue of Mus musculus in NPYR administered lungs and effect of isolated flavonoid 3,6-dihydroxy-(3’,4’,7’-trimethoxyphenyl)-chromen-4-one-7-glucoside (ITC) from experimental plant Indigofera tinctorial. Post treatment with isolated compound significantly restored the abnormal symptoms and changes in pulmonary tissue. Transverse section of mouse lung in control animals appeared as a thin lace. Histologically, most of the lung was arranged as alveoli which were thin walled structures made up of single layered squamous epithelial cells. In the transverse section of lung at 100 X will clearly show the component of alveoli, surround by a thin layer of connective tissue and blood vessels. Smaller bronchioles were lined by cuboidal epithelial cells while larger bronchioles were lined by ciliated columnar epithelium layer while in NPYR intoxicated lungs signs of vast pulmonary damages and carcinogenesis as alveolar damage, necrosis, DADs or defused alveolar damages hyperplasia, metaplasia, dysplasia and next stage of carcinogenesis were revealed. Treatment with ITC showed the significant positive changes in the lung tissue due to the side hydroxyl and methoxy groups in its structure which help in combating oxidative injuries and give protection from the free radicals generated during the metabolism of NPYR in body. Thus, histopathological analysis confirms the development of the cancerous conditions in the lung tissue in mice model and the protective effects of ITC.

Keywords: flavonoid, histopathology, Indigofera tinctoria, lung

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Authors: Nathalie Bolding, Marta Montero, Joaquim Cevallos, Juan F. Martin-Lazaro

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Background: Inhaled epoprostenol (iEPO) have been shown to improve PaO2:FiO2 (PF) in combination with bronchodilators (BD). However, there is not an available device to deliver these two therapies concomitantly. We describe a new method to provide this therapy successfully. Objective: To evaluate the response to continuous nebulization of iEPO and intermittent nebulization of Salbutamol/Ipratropium bromide in adults with severe respiratory failure through a double mesh nebulisation in tandem. Methods: This observational study included two mechanical ventilated adults under hourly ventilatory, gasometrical and clinical measurements during 48h. Both had severe respiratory failure treated with continuous iEPO (50 – 200 micrograms/h) and BD (Salbutamol 2.5 mg and Ipratropium bromide 500 mcg every 6 hours) through double mesh nebulisation (Aerogen solo®) placed in tandem in the dry side of the humidificator. The primary endpoints were the variables associated with a positive response to this tandem nebulised therapy (PaFiO2 index, ROX index). Secondary endpoints were laboratory (ABG) clinical and ventilatory variables. Statistical analysis (SPSS v29) included linear regression and ANOVA. Results: The patients included (n=2) survived, both extubated, one after ECMO therapy. Severe acute respiratory failure had a positive response rate to continuous iEPO and intermittent BD: PaFiO2 increased (7.40 to 30.91; P75: 27%) as well as ROX index (2.91 to 11.43; P75: 33%). There was a linear correlation of improvement between iEPO with PaFiO2 (ANOVA, r=0.393, p<0.002) and ROX (r=0.419, p<0.001). iEPO+BD therapy did not show any complications. Conclusion: Continuous and intermittent mesh tandem nebulisation can be effectively delivered with this method with a positive effect in ventilatory parameters without observed complications. Randomised studies will be able to provide reassurance in this new therapy.

Keywords: tandem, mesh, nebulisers, pulmonary, vasoldilators, bronchodilators, respiratory, failure

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Authors: Katharigatta N. Venugopala, Fernando Albericio, Bander E. Al-Dhubiab, T. Govender

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Recent years have witnessed a renaissance in the field of peptides that are obtained from various natural sources such as many bacteria, fungi, plants, seaweeds, vertebrates, invertebrates and have been reported for various pharmacological properties such as anti-TB, anticancer, antimalarial, anti-inflammatory, anti-HIV, antibacterial, antifungal, and antidiabetic, activities. In view of the pharmacological significance of natural peptides, serious research efforts of many scientific groups and pharmaceutical companies have consequently focused on them to explore the possibility of developing their potential analogues as therapeutic agents. Solid phase and solution phase peptide synthesis are the two methodologies currently available for the synthesis of natural or synthetic linear or cyclic depsi-peptides. From a synthetic point of view, there is no doubt that the solid-phase methodology gained added advantages over solution phase methodology in terms of simplicity, purity of the compound and the speed with which peptides can be synthesised. In the present study total synthesis, purification and structural elucidation of analogues of natural anti-TB cyclic depsi-peptides such as depsidomycin, massetolides and viscosin has been attempted by solid phase method using standard Fmoc protocols and finally off resin cyclization in solution phase method. In case of depsidomycin, synthesis of linear peptide on solid phase could not be achieved because of two turn inducing amino acids in the peptide sequence, but total synthesis was achieved by convergent solid phase peptide synthesis followed by cyclization in solution phase method. The title compounds obtained were in good yields and characterized by NMR and HRMS. Anti-TB results revealed that the potential title compound exhibited promising activity at 4 µg/mL against H37Rv and 16 µg/mL against MDR strains of tuberculosis.

Keywords: total synthesis, cyclic depsi-peptides, anti-TB activity, tuberculosis

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Authors: Saboor Saeed, Chunming Jiang

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Eosinophilic Granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome, is a rare systemic vasculitis of small and medium-sized vessels that primarily develops in middle-aged individuals. It is characterized by asthma, blood eosinophilia, and extra pulmonary manifestations. In childhood, EGPA is extremely rare. Pulmonary and cardiac involvement is predominant in pediatric EGPA, and mortality is substantial. Generally, EGPA will develop in three stages: a) The allergic phase is commonly associated with asthma, allergic rhinitis, and sinusitis, b) the eosinophilic phase, in which the main pathology is related to the infiltration of eosinophilic organs, i.e., lung, heart, and gastrointestinal system, c) vasculitis phase involved purpura, peripheral neuropathy, and some constitutional symptoms. The key to the treatment of EGPA lies in the early diagnosis of the disease. Early application of glucocorticoids and immunosuppressants can improve symptoms and the overall prognosis of EGPA. Case Description: We presented a case of an 8-year-old boy with a history of short asthma, marked eosinophilia, and multi-organ involvement. The extremely high eosinophil level in the blood (72.50%) prompted the examination of eosinophilic leukemia before EGPA diagnosis was made. Subsequently, this disease was successfully treated. This case report shows a typical case of CSS in childhood because of the extreme eosinophilia. It emphasizes the importance of EGPA is a life-threatening cause of children's eosinophilia. Conclusion: EGPA in children has unique clinical, imaging, and histological characteristics different from those of adults. In pediatric patients, the development and diagnosis of systemic symptoms are often delayed, mainly occurring in the eosinophilic phase, which will lead to specific manifestations. At the same time, we cannot detect a genetic relationship related to EGPA.

Keywords: Churg Strauss syndrome, asthma, vasculitis, hypereosinophilia, eosinophilic granulomatosis polyangiitis

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Authors: Paras Agarwal

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Background: Initially believed to be rare, metastases to the eye are the most common ocular malignancy. The choroid’s high perfusion rate not only makes it the most susceptible ocular site for tumour seeding, but also promotes its growth. The cancers most frequently responsible for choroidal metastases originate from the breast and lung, although a significant proportion have unidentified primaries at the time of presentation. Case Presentation: This case report describes a 34 year old female presenting to the ophthalmology department with a one month history of painless distorted vision. On fundus examination, she was noted to have bilateral choroidal lesionsand subsequently underwent a comprehensive diagnostic work-up. The patient was diagnosed with metastatic pulmonary adenocarcinoma, despite lacking conventional risk factors. As she was found to have a mutation in EGFR, the patient was commenced on tyrosine-kinase inhibition with afatinib. The choroidal lesions regressed with a significant improvement in visual acuity and a dramatic anatomical reduction of the choroidal masses. Conclusions: Our case demonstrates the importance of considering metastases as a differential diagnosis for choroidal lesions. Appropriate and thorough history-taking, examination and investigations may be required in order to deduce the underlying cause. Our case is unusual in view of the choroidal lesion being the primary manifestation of metastatic lung cancer in a young patient with no known risk factors. Early recognition of choroidal metastases is important as it is often the first sign of tumour dissemination and will prompt earlier treatment with systemic medications such as chemotherapy, immunotherapy, targeted therapy or hormonal therapy. Our case report also demonstrates the efficacy of afatinib for the treatment of choroidal metastases, with morphological and functional improvements observed with regard to the choroidal metastatic tumour.

Keywords: choroidal neoplasm, choroidal naevus, pulmonary adenocarcinoma, metastases, lung cancer

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Authors: Sharique Ahmed, Khushtar Anwar Salman

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Alpha-1-antitrypsin (AAT) is a major plasma serine protease inhibitor (SERPIN). Hereditary AAT deficiency is one of the common diseases in some part of the world. AAT is mainly produced in the liver and functions to protect the lung against proteolytic damage (e.g., from neutrophil elastase) acting as the major inhibitor for neutrophil elastase. α (1)-Antitrypsin (AAT) deficiency is an under recognized genetic condition that affects approximately 1 in 2,000 to 1 in 5,000 individuals and predisposes to liver disease and early-onset emphysema. Not only does α-1-antitrypsin deficiency lead to disabling syndrome of pulmonary emphysema, there are other disorders too which include ANCA (antineutrophilic cytoplasmic antibody) positive Wegener's granulomatosis, diffuse bronchiectasis, necrotizing panniculitis in α-1-antitrypsin phenotype (S), idiopathic pulmonary fibrosis and steroid dependent asthma. Augmentation therapy with alpha-1 antitrypsin (AAT) from human plasma has been available for specific treatment of emphysema due to AAT deficiency. Apart from this several observations have also suggested a role for endogenous suppressors of HIV-1, alpha-1 antitrypsin (AAT) has been identified to be one of those. In view of its varied important role in humans, serum from a mammalian source was chosen for the isolation and purification. Studies were performed on the homogeneous fraction. This study suggests that the buffalo serum α-1-antritrypsin has characteristics close to ovine, dog, horse and more importantly to human α-1-antritrypsin in terms of its hydrodynamic properties such as molecular weight, carbohydrate content, etc. The similarities in the hydrodynamic properties of buffalo serum α-1-antitrypsin with other sources of mammalian α-1-antitrypsin mean that it can be further studied and be a potential source for "augmentation therapy", as well as a source of AAT replacement therapy to raise serum levels above the protective threshold. Other parameters like the amino acid sequence, the effect of denaturants, and the thermolability or thermostability of the inhibitor will be the interesting basis of future studies on buffalo serum alpha-1 antitrypsin (AAT).

Keywords: α-1-antitrypsin, augmentation therapy , hydrodynamic properties, serine protease inhibitor

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Authors: Maryam Radan, Fereshteh Nejad Dehbashi, Vahid Bayati, Mahin Dianat, Seyyed Ali Mard, Zahra Mansouri

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Pulmonary emphysema is a pathological respiratory condition identified by alveolar destruction which leads to limitation of airflow and diminished lung function. A substantial body of evidence suggests that mesenchymal stem cells (MSCs) have the ability to induce tissue repair primarily through a paracrine effect. In this study, we aimed to determine the efficacy of Intratracheal adipose-derived mesenchymal stem cells (ADSCs) therapy in comparison to this approach with that of Intravenous (Systemic) therapy. Fifty adult male Sprague–Dawley rats weighing between 180 and 200 g were used in this experiment. The animals were randomized to Control groups (Intratracheal or Intravenous vehicle), Elastase group (intratracheal administration of porcine pancreatic elastase; 25 U/kg on day 0 and day 10th), Elastase+Intratracheal ADSCs therapy (1x107 Cells, on day 28) and Elastase+Systemic ADSCs therapy (1x107 Cells, on day 28). The rats which not subjected to any treatment, considered as the control. All rats were sacrificed 3 weeks later. Morphometric findings in lung tissues (Mean linear intercept) confirmed the establishment of the emphysema model via alveolar disruption. Contrarily, ADSCs administration partially restored alveolar architecture. These results were associated with improving arterial oxygenation, reducing lung edema, and decreasing lung inflammation with higher significant effects in the Intratracheal therapy route. These results documented that the efficacy of intratracheal ADSCs was comparable with intravenous ADSCs therapy. Accordingly, the obtained data suggested that intratracheal delivery of ADSCs would enhance lung repair in pulmonary emphysema. Moreover, this method provides benefits over a systemic administration, such as the reduction of cell number and the low risk to engraft other organs.

Keywords: mesenchymal stem cell, emphysema, Intratracheal, systemic

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Authors: Vandana Mohan, Ashwani Koul

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Aim: To evaluate the potential of Aqueous Tinospora cordifolia stem extract (Aq.Tc) and Arabinogalactan (AG) on pulmonary carcinogenesis and associated tumor markers. Background: Lung cancer is one of the most frequent malignancy with high mortality rate due to limitation of early detection resulting in low cure rates. Current research effort focuses on identifying some blood-based biomarkers like CEA, ctDNA and LDH which may have potential to detect cancer at an early stage, evaluation of therapeutic response and its recurrence. Medicinal plants and their active components have been widely investigated for their anticancer potentials. Aqueous preparation of T. Cordifolia extract is enriched in the polysaccharide fraction i.e., AG when compared with other types of extract. Moreover, reports are available of polysaccharide fraction of T. Cordifolia in in vitro lung cancer models which showed profound anti-metastatic activity against these cell lines. However, not much has been explored about its effect in in vivo lung cancer models and the underlying mechanism involved. Experimental Design: Mice were randomly segregated into six groups. Group I animals served as control. Group II animals were administered with Aq. Tc extract (200 mg/kg b.w.) p.o.on the alternate days. Group III animals were fed with AG (7.5 mg/kg b.w.) p.o. on the alternate days (thrice a week). Group IV animals were installed with Benzo(a)pyrene (50 mg/kg b.w.), i.p. twice within an interval of two weeks. Group V animals received Aq. Tc extract as in group II along with it B(a)P was installed after two weeks of Aq. Tc administration following the same protocol as for group IV. Group VI animals received AG as in group III along with it B(a)P was installed after two weeks of AG administration. Results: Administration of B(a)P to mice resulted in increased tumor incidence, multiplicity and pulmonary somatic index with concomitant increase in serum/plasma markers like CEA, ctDNA, LDH and TNF-α.Aq.Tc and AG supplementation significantly attenuated these alterations at different stages of tumorigenesis thereby showing potent anti-cancer effect in lung cancer. A pronounced decrease in serum/plasma markers were observed in animals treated with Aq.Tc as compared to those fed with AG. Also, extensive hyperproliferation of alveolar epithelium was prominent in B(a)P induced lung tumors. However, treatment of Aq.Tc and AG to lung tumor bearing mice exhibited reduced alveolar damage evident from decreased number of hyperchromatic irregular nuclei. A direct correlation between the concentration of tumor markers and the intensity of lung cancer was observed in animals bearing cancer co-treated with Aq.Tc and AG. Conclusion: These findings substantiate the chemopreventive potential of Aq.Tc and AG against lung tumorigenesis. Interestingly, Aq.Tc was found to be more effective in modulating the cancer as reflected by various observations which may be attributed to the synergism offered by various components of Aq.Tc. Further studies are in progress to understand the underlined mechanism in inhibiting lung tumorigenesis by Aq.Tc and AG.

Keywords: Arabinogalactan, Benzo(a)pyrene B(a)P, carcinoembryonic antigen (CEA), circulating tumor DNA (ctDNA), lactate dehydrogenase (LDH), Tinospora cordifolia

Procedia PDF Downloads 157

Authors: Nicholas Bayfield, Liam Bibo, Charley Budgeon, Robert Larbalestier, Tom Briffa

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Introduction: Stress hyperglycaemia is common following cardiac surgery. Its optimal management is uncertain and may differ by diabetic status. This study assesses the in-hospital glycaemic management of cardiac surgery patients and associated postoperative outcomes. Methods: A retrospective cohort analysis of all patients undergoing cardiac surgery at Fiona Stanley Hospital from February 2015 to May 2019 was undertaken. Management and outcomes of hyperglycaemia following cardiac surgery were assessed. Follow-up was assessed to 1 year postoperatively. Multivariate regression modelling was utilised. Results: 1050 non-diabetic patients and 689 diabetic patients were included. In the non-diabetic cohort, patients with mild (peak blood sugar level [BSL] < 14.3), transient stress hyperglycaemia managed without insulin were not at an increased risk of wound-related morbidity (P=0.899) or mortality at 1 year (P=0.483). Insulin management was associated with wound-related readmission to hospital (P=0.004) and superficial sternal wound infection (P=0.047). Prolonged or severe stress hyperglycaemia was predictive of hospital re-admission (P=0.050) but not morbidity or mortality (P=0.546). Diabetes mellitus was an independent risk factor 1-year mortality (OR; 1.972 [1.041–3.736], P=0.037), graft harvest site wound infection (OR; 1.810 [1.134–2.889], P=0.013) and wound-related readmission (OR; 1.866 [1.076–3.236], P=0.026). In diabetics, postoperative peak BSL > 13.9mmol/L was predictive of graft harvest site infections (OR; 3.528 [1.724-7.217], P=0.001) and wound-related readmission OR; 3.462 [1.540-7.783], P=0.003) regardless of modality of management. A peak BSL of 10.0-13.9 did not increase the risk of morbidity/mortality compared to a peak BSL of < 10.0 (P=0.557). Diabetics with a peak BSL of 13.9 or less did not have significantly increased morbidity/mortality outcomes compared to non-diabetics (P=0.418). Conclusion: In non-diabetic patients, transient mild stress hyperglycaemia following cardiac surgery does not uniformly require treatment. In diabetic patients, postoperative hyperglycaemia with peak BSL exceeding 13.9mmol/L was associated with wound-related morbidity and hospital readmission following cardiac surgery.

Keywords: cardiac surgery, pulmonary embolism, pulmonary embolectomy, cardiopulmonary bypass

Procedia PDF Downloads 134

Authors: Uliana N. Tumanova, Sergey M. Voevodin, Veronica A. Sinitsyna, Alexandr I. Shchegolev

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An important part of forensic and autopsy research in perinatology is the answer to the question of life and stillbirth. Postmortem magnetic resonance imaging (MRI) is an objective non-invasive research method that allows to store data for a long time and not to exhume the body to clarify the diagnosis. The purpose of the research is to study the possibilities of a postmortem MRI to determine the stillbirth and death of a newborn who had spontaneous breathing and died on the first day after birth. MRI and morphological data of a study of 23 stillborn bodies, prenatally dead at a gestational age of 22-39 weeks (Group I) and the bodies of 16 newborns who died from 2 to 24 hours after birth (Group II) were compared. Before the autopsy, postmortem MRI was performed on the Siemens Magnetom Verio 3T device in the supine position of the body. The control group for MRI studies consisted of 7 live newborns without lung disease (Group III). On T2WI in the sagittal projection was measured MR-signal intensity (SI) in the lung tissue (L) and shoulder muscle (M). During the autopsy, a pulmonary swimming test was evaluated, and macro- and microscopic studies were performed. According to the postmortem MRI, the highest values of mean SI of the lung (430 ± 27.99) and of the muscle (405.5 ± 38.62) on T2WI were detected in group I and exceeded the corresponding value of group II by 2.7 times. The lowest values were found in the control group - 77.9 ± 12.34 and 119.7 ± 6.3, respectively. In the group II, the lung SI was 1.6 times higher than the muscle SI, whereas in the group I and in the control group, the muscle SI was 2.1 times and 1.8 times larger than the lung. On the basis of clinical and morphological data, we calculated the formula for determining the breathing index (BI) during postmortem MRI: BI = SIL x SIM / 100. The mean value of BI in the group I (1801.14 ± 241.6) (values ranged from 756 to 3744) significantly higher than the corresponding average value of BI in the group II (455.89 ± 137.32, p < 0.05) (305-638.4). In the control group, the mean BI value was 91.75 ± 13.3 (values ranged from 53 to 154). The BI with the results of pulmonary swimming tests and microscopic examination of the lungs were compared. The boundary value of BI for the differential diagnosis of stillborn and newborn death was 700. Using the postmortem MRI allows to differentiate the stillborn with the death of the breathing newborn.

Keywords: lung, newborn, postmortem MRI, stillborn

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Authors: A. Abubakar, A. Parsa, S. Walker

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Despite advances made in the diagnosis and management of drug-sensitive tuberculosis (TB) over the past decades, treatment of multidrug-resistant tuberculosis (MDR-TB) remains challenging and complex particularly in high burden countries including Nigeria. Treatment of MDR-TB is cost-prohibitive with success rate generally lower compared to drug-sensitive TB and if care is not taken it may become the dominant form of TB in future with many treatment uncertainties and substantial morbidity and mortality. Addressing these challenges requires collaborative efforts thorough sustained researches to evaluate the current treatment guidelines, particularly in high burden countries and prevent progression of resistance. To our best knowledge, there has been no research exploring the acceptability, effectiveness, and cost-effectiveness of community-based-MDR-TB treatment model in Nigeria, which is among the high burden countries. The previous similar qualitative study looks at the home-based management of MDR-TB in rural Uganda. This research aimed to explore patient’s views and acceptability of community-based-MDR-TB treatment model and to evaluate and compare the effectiveness and cost-effectiveness of community-based versus hospital-based MDR-TB treatment model of care from the Nigerian perspective. Knowledge of patient’s views and acceptability of community-based-MDR-TB treatment approach would help in designing future treatment recommendations and in health policymaking. Accordingly, knowledge of effectiveness and cost-effectiveness are part of the evidence needed to inform a decision about whether and how to scale up MDR-TB treatment, particularly in a poor resource setting with limited knowledge of TB. Mixed methods using qualitative and quantitative approach were employed. Qualitative data were obtained using in-depth semi-structured interviews with 21 MDR-TB patients in Nigeria to explore their views and acceptability of community-based MDR-TB treatment model. Qualitative data collection followed an iterative process which allowed adaptation of topic guides until data saturation. In-depth interviews were analyzed using thematic analysis. Quantitative data on treatment outcomes were obtained from medical records of MDR-TB patients to determine the effectiveness and direct and indirect costs were obtained from the patients using validated questionnaire and health system costs from the donor agencies to determine the cost-effectiveness difference between community and hospital-based model from the Nigerian perspective. Findings: Some themes have emerged from the patient’s perspectives indicating preference and high acceptability of community-based-MDR-TB treatment model by the patients and mixed feelings about the risk of MDR-TB transmission within the community due to poor infection control. The result of the modeling from the quantitative data is still on course. Community-based MDR-TB care was seen as the acceptable and most preferred model of care by the majority of the participants because of its convenience which in turn enhanced recovery, enables social interaction and offer more psychosocial benefits as well as averted productivity loss. However, there is a need to strengthen this model of care thorough enhanced strategies that ensure guidelines compliance and infection control in order to prevent the progression of resistance and curtail community transmission.

Keywords: acceptability, cost-effectiveness, multidrug-resistant TB treatment, community and hospital approach

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Authors: Sawang Saenghirunvattana, Chao Saenghirunvattana, Maria Christina Gonzales, Wilai Srimuk, Chitchamai Siangpro, Kritsana Sutthisri

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Introduction: Thailand is one of the fastest growing countries in Asia. It has emerged from agricultural to industrialized economy. Work places have shifted from farms to factories, offices and streets were employees are exposed to certain chemicals and pollutants causing occupational diseases particularly asthma. Work-related diseases are major concern and many studies have been published to demonstrate certain professions and their exposures that elevate the risk of asthma. Workers who exhibit coughing, wheezing and difficulty of breathing are brought to a health care setting where Pulmonary Function Test (PFT) is performed and based from results, they are then diagnosed of asthma. These patients, known to have occupational asthma eventually get well when removed from the exposure of the environment. Our study, focused on performing PFT or specific challenge test in diagnosing workers of occupational asthma with them executing the test within their workplace, maintaining the environment and their daily exposure to certain levels of chemicals and pollutants. This has provided us with an understanding and reliable diagnosis of occupational asthma. Objective: To identify the prevalence of Thai workers who develop asthma caused by exposure to pollutants and chemicals from their working environment by conducting interview and performing PFT or specific challenge test in their work places. Materials and Methods: This study was performed from January-March 2015 in Bangkok, Thailand. The percentage of abnormal symptoms of 940 workers in 5 different areas (factories of plastic, fertilizer, animal food, office and streets) were collected through a questionnaire. The demographic information, occupational history, and the state of health were determined using a questionnaire and checklists. PFT was executed in their work places and results were measured and evaluated. Results: Pulmonary Function test was performed by 940 participants. The specific challenge test was done in factories of plastic, fertilizer, animal food, office environment and on the streets of Thailand. Of the 100 participants working in the plastic industry, 65% complained of having respiratory symptoms. None of them had an abnormal PFT. From the participants who worked with fertilizers and are exposed to sulfur dioxide, out of 200 participants, 20% complained of having symptoms and 8% had abnormal PFT. The 300 subjects working with animal food reported that 45% complained of respiratory symptoms and 15% had abnormal PFT results. From the office environment where there is indoor pollution, Out of 140 subjects, 7% had symptoms and 4% had abnormal PFT. The 200 workers exposed to traffic pollution, 24% reported respiratory symptoms and 12% had abnormal PFT. Conclusion: We were able to identify and diagnose participants of occupational asthma through their abnormal lung function test done at their work places. The chemical agents and exposures were determined therefore effective management of workers with occupational asthma were advised to avoid further exposure for better chances of recovery. Further studies identifying the risk factors and causative agents of asthma in workplaces should be developed to encourage interventional strategies and programs that will prevent occupation related diseases particularly asthma.

Keywords: occupational asthma, pulmonary function test, specific challenge test, Thailand

Procedia PDF Downloads 280

Authors: Ayman K. El Essawy, Amal M. Hosny, Hala M. Abu Shady

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The rapid detection of TB and drug resistance, both optimizes treatment and improves outcomes. In the current study, respiratory specimens were collected from 155 patients. Conventional susceptibility testing and MIC determination were performed for rifampicin (RIF) and isoniazid (INH). Genotype MTBDRplus assay, which is a molecular genetic assay based on the DNA-STRIP technology and specific gene sequencing with primers for rpoB, KatG, and mab-inhA genes were used to detect mutations associated with resistance to rifampicin and isoniazid. In comparison to other categories, most of rifampicin resistant (61.5%) and isoniazid resistant isolates (47.1%) were from patients relapsed in treatment. The genotypic profile (using Genotype MTBDRplus assay) of multi-drug resistant (MDR) isolates showed missing of katG wild type 1 (WT1) band and appearance of mutation band katG MUT2. For isoniazid mono-resistant isolates, 80% showed katG MUT1, 20% showed katG MUT1, and inhA MUT1, 20% showed only inhA MUT1. Accordingly, 100% of isoniazid resistant strains were detected by this assay. Out of 17 resistant strains, 16 had mutation bands for katG distinguished high resistance to isoniazid. The assay could clearly detect rifampicin resistance among 66.7% of MDR isolates that showed mutation band rpoB MUT3 while 33.3% of them were considered as unknown. One mono-resistant rifampicin isolate did not show rifampicin mutation bands by Genotype MTBDRplus assay, but it showed an unexpected mutation in Codon 531 of rpoB by DNA sequence analysis. Rifampicin resistance in this strain could be associated with a mutation in codon 531 of rpoB (based on molecular sequencing), and Genotype MTBDRplus assay could not detect the associated mutation. If the results of Genotype MTBDRplus assay and sequencing were combined, this strain shows hetero-resistance pattern. Gene sequencing of eight selected isolates, previously tested by Genotype MTBDRplus assay, could detect resistance mutations mainly in codon 315 (katG gene), position -15 in inhA promotes gene for isoniazid resistance and codon 531 (rpoB gene) for rifampicin resistance. Genotyping techniques allow distinguishing between recurrent cases of reinfection or reactivation and supports epidemiological studies.

Keywords: M. tuberculosis, rpoB, KatG, inhA, genotype MTBDRplus

Procedia PDF Downloads 115

Authors: Maryam Fallahpoor, Biswajeet Pradhan

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Background: Artificial intelligence (AI) serves as a valuable tool in mitigating the scarcity of human resources required for the evaluation and categorization of vast quantities of medical imaging data. When AI operates with optimal precision, it minimizes the demand for human interpretations and, thereby, reduces the burden on radiologists. Among various AI approaches, deep learning (DL) stands out as it obviates the need for feature extraction, a process that can impede classification, especially with intricate datasets. The advent of DL models has ushered in a new era in medical imaging, particularly in the context of COVID-19 detection. Traditional 2D imaging techniques exhibit limitations when applied to volumetric data, such as Computed Tomography (CT) scans. Medical images predominantly exist in one of two formats: neuroimaging informatics technology initiative (NIfTI) and digital imaging and communications in medicine (DICOM). Purpose: This study aims to employ DL for the classification of COVID-19-infected pulmonary patients and normal cases based on 3D CT scans while investigating the impact of image format. Material and Methods: The dataset used for model training and testing consisted of 1245 patients from IranMehr Hospital. All scans shared a matrix size of 512 × 512, although they exhibited varying slice numbers. Consequently, after loading the DICOM CT scans, image resampling and interpolation were performed to standardize the slice count. All images underwent cropping and resampling, resulting in uniform dimensions of 128 × 128 × 60. Resolution uniformity was achieved through resampling to 1 mm × 1 mm × 1 mm, and image intensities were confined to the range of (−1000, 400) Hounsfield units (HU). For classification purposes, positive pulmonary COVID-19 involvement was designated as 1, while normal images were assigned a value of 0. Subsequently, a U-net-based lung segmentation module was applied to obtain 3D segmented lung regions. The pre-processing stage included normalization, zero-centering, and shuffling. Four distinct 3D CNN models (ResNet152, ResNet50, DensNet169, and DensNet201) were employed in this study. Results: The findings revealed that the segmentation technique yielded superior results for DICOM images, which could be attributed to the potential loss of information during the conversion of original DICOM images to NIFTI format. Notably, ResNet152 and ResNet50 exhibited the highest accuracy at 90.0%, and the same models achieved the best F1 score at 87%. ResNet152 also secured the highest Area under the Curve (AUC) at 0.932. Regarding sensitivity and specificity, DensNet201 achieved the highest values at 93% and 96%, respectively. Conclusion: This study underscores the capacity of deep learning to classify COVID-19 pulmonary involvement using real 3D hospital data. The results underscore the significance of employing DICOM format 3D CT images alongside appropriate pre-processing techniques when training DL models for COVID-19 detection. This approach enhances the accuracy and reliability of diagnostic systems for COVID-19 detection.

Keywords: deep learning, COVID-19 detection, NIFTI format, DICOM format

Procedia PDF Downloads 42

Authors: Sheikha Turki Alketbi

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Objectives: 1. Documenting the spontaneous resolution of AML following the initiation of anti-TB therapy. 2. Presenting an uncommon type of relapse in Acute Myeloid Leukemia. 3. Highlighting the role of immune markers in the diagnosis of Leukemia cutis. 4. Exploring and highlighting the possibility of skin relapse as the exclusive manifestation, even when skin involvement is known secondary manifestation in AML. Background: Spontaneous remission of Acute Myeloid Leukemia (AML) is a rare phenomenon that has only been reported in some case reports, usually following severe infections. Some studies have described the occurrence of tuberculosis (TB) infection with AML, usually after starting chemotherapy. Spontaneous resolution of AML after starting anti TB therapy (ATT), without starting chemotherapy has never been described in the literature. Moreover, Leukemia cutis is another rare skin manifestation of Acute Myeloid Leukemia as a result of infiltration of the skin or subcutaneous tissue by leukemic cells, in which can present during, precedes, after or independently of systemic leukemia. Methods: Here, we present a case of a 13-year-old male who presented with fever, weight loss, lethargy, epistaxis, bruising and dry cough and was later diagnosed with AML. Before initiating leukemia treatment, the patient was tested for TB and was found to have active TB infection. His leukemia treatment was postponed to clear the TB infection and he was commenced on ATT. Two months later, repeat blood film and bone marrow biopsy showed resolution of his AML. The patient remained in remission for 1 month, after which he presented with symmetrical blue purple well-defined round indurated plaques on the chest and thighs. Our differentials were leukemia cutis and Kaposi sarcoma. Results: Skin Biopsy with immune markers done, showed a picture of Acute Myeloid Leukemia. Immunohistochemistry (IHC) showed neoplastic cells diffusely and strongly positive for LCA, CD2, CD31, MPO, CD117, Lysozymes and TDT, and moderately positive for CD34, CD99, CD43 and CD6 And patchy for CD68. Ki67 showed 60% proliferation index. They were negative for the remaining markers. This suggested acute myeloid leukemia (AML). Conclusion: In summary, we present a rare case of TB with AML that resolved after treatment of TB with ATT but relapsed later as leukemia cutis. While skin involvement might occur as a secondary manifestation of AML, Skin relapse could be the only one.

Keywords: Leukemia cutis, Leukemia relapse, Acute Myeloid Leukemia, spontaneous resolution of AML

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Authors: Y. Landkocz, C. Lepers, P.J. Martin, B. Fougère, F. Roy Saint-Georges. A. Verdin, F. Cazier, F. Ledoux, D. Courcot, F. Sichel, P. Gosset, P. Shirali, S. Billet

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In 2013, the International Agency for Research on Cancer (IARC) classified air pollution and fine particles as carcinogenic to humans. Causal relationships exist between elevated ambient levels of airborne particles and increase of mortality and morbidity including pulmonary diseases, like lung cancer. However, due to a double complexity of both physicochemical Particulate Matter (PM) properties and tumor mechanistic processes, mechanisms of action remain not fully elucidated. Furthermore, because of several common properties between air pollution PM and tobacco smoke, like the same route of exposure and chemical composition, potential mechanisms of synergy could exist. Therefore, smoking could be an aggravating factor of the particles toxicity. In order to identify some mechanisms of action of particles according to their size, two samples of PM were collected: PM0.03 2.5 and PM0.33 2.5 in the urban-industrial area of Dunkerque. The overall cytotoxicity of the fine particles was determined on human bronchial cells (BEAS-2B). Toxicological study focused then on the metabolic activation of the organic compounds coated onto PM and some genetic and epigenetic changes induced on a co-culture model of BEAS-2B and alveolar macrophages isolated from bronchoalveolar lavages performed in smokers and non-smokers. The results showed (i) the contribution of the ultrafine fraction of atmospheric particles to genotoxic (eg. DNA double-strand breaks) and epigenetic mechanisms (eg. promoter methylation) involved in tumor processes, and (ii) the influence of smoking on the cellular response. Three main conclusions can be discussed. First, our results showed the ability of the particles to induce deleterious effects potentially involved in the stages of initiation and promotion of carcinogenesis. The second conclusion is that smoking affects the nature of the induced genotoxic effects. Finally, the in vitro developed cell model, using bronchial epithelial cells and alveolar macrophages can take into account quite realistically, some of the existing cell interactions existing in the lung.

Keywords: air pollution, fine and ultrafine particles, genotoxic and epigenetic alterations, smoking

Procedia PDF Downloads 317

Authors: Jianming Cai

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Exposure to ionizing radiation causes severe damage to human body and an safe and effective radioprotector is urgently required for alleviating radiation damage. In 2008, flagellin, an agonist of TLR5, was found to exert radioprotective effects on radiation injury through activating NF-kB signaling pathway. From then, the radioprotective effects of TLR ligands has shed new lights on radiation protection. CpG-ODN is an unmethylated oligonucleotide which activates TLR9 signaling pathway. In this study, we demonstrated that CpG-ODN has therapeutic effects on radiation injuries induced by γ ray and 12C6+ heavy ion particles. Our data showed that CpG-ODN increased the survival rate of mice after whole body irradiation and increased the number of leukocytes as well as the bone marrow cells. CpG-ODN also alleviated radiation damage on intestinal crypt through regulating apoptosis signaling pathway including bcl2, bax, and caspase 3 etc. By using a radiation-induced pulmonary fibrosis model, we found that CpG-ODN could alleviate structural damage, within 20 week after whole–thorax 15Gy irradiation. In this model, Th1/Th2 imbalance induced by irradiation was also reversed by CpG-ODN. We also found that TGFβ-Smad signaling pathway was regulated by CpG-ODN, which accounts for the therapeutic effects of CpG-ODN in radiation-induced pulmonary injury. On another hand, for high LET radiation protection, we investigated protective effects of CpG-ODN against 12C6+ heavy ion irradiation and found that after CpG-ODN treatment, the apoptosis and cell cycle arrest induced by 12C6+ irradiation was reduced. CpG-ODN also reduced the expression of Bax and caspase 3, while increased the level of bcl2. Then we detected the effect of CpG-ODN on heavy ion induced immune dysfunction. Our data showed that CpG-ODN increased the survival rate of mice and also the leukocytes after 12C6+ irradiation. Besides, the structural damage of immune organ such as thymus and spleen was also alleviated by CpG-ODN treatment. In conclusion, we found that TLR9 ligand, CpG-ODN reduced radiation injuries in response to γ ray and 12C6+ heavy ion irradiation. On one hand, CpG-ODN inhibited the activation of apoptosis induced by radiation through regulating bcl2, bax and caspase 3. On another hand, through activating TLR9, CpG-ODN recruit MyD88-IRAK-TRAF6 complex, activating TAK1, IRF5 and NF-kB pathway, and thus alleviates radiation damage. This study provides novel insights into protection and therapy of radiation damages.

Keywords: TLR9, CpG-ODN, radiation injury, high LET radiation

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Authors: Nuruddin Mohammod Zahangir, Syed Tanvir Ahmady, Firoz Ahmed, Mainul Kabir, Tamjid Mohammad Najmus Sakib Khan, Nazmul Hossain, Niaz Ahmed, Madhava Janardhan Naik

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The management of combined Coronary Artery Disease and Peripheral Vascular Disease is a challenge and brings with it numerous clinical dilemmas.The 56 year old gentleman presented to our department with significant triple vessel disease with occluded lower end of aorta just before bifurcation and bilateral superficial femoral arteries. Operation was done on 11.03.14. The The Left Internal Mammary Artery (LIMA) and the Right Internal Mammary Artery (RIMA) were harvested in skeletonized manner. The free RIMA was then anastomosed with LIMA to make LIMA-RIMA Y. Cardio Pulmonary Bypass was then established and coronary artery bypass grafts performed. LIMA was anastomosed to the Left Anterior Descending artery. RIMA was anastomosed to Posterior Descending Artery, 1st and 2nd Obtuse Marginal arteries in a sequential manner. Abdomen was opened by midline incision. The infrarenal aorta exposed and was found to be severely diseased. A Vascular Clamp was applied infrarenally, aortotomy done and limited endarterectomy performed. An end-to-side anastomosis was done with upper end of PTFE synthetic Y-graft (14/7 mm) to the infarenal Aorta and the Clamp released. Good flow noted in both limbs of the graft. Patient was then slowly weaned off from Cardio Pulmonary Bypass without difficulty. The distal two limbs of the Y graft were passed to the groin through retroperitoneal tunnels and anastomosed end-to-side with the common femoral arteries. Saphenous vein was interposed between common femoral and popliteal arteries bilaterally through subfascial tunnels in both thigh. On 12th postoperative day he was discharged from hospital in good general condition. Follow up after 3 months of operation the patient is doing good and free of chest pain and claudication pain.

Keywords: total arterial, coronary revascularization, aorto-bifemoral bypass, bifemoro-bipopliteal bypass

Procedia PDF Downloads 436

Authors: D. Densenbal, Ts. Naidansuren, M. Oyunchimeg, Ts. Manaljav, D. Udval, L. Khosbayar, Kh. Solongo, D. Ichinnorov, B. Solongo

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Background: The rapid economic growth and to the common use of smoky fuel such as coal in the small traditional houses (Ger) in Mongolia is worsening its air pollution problem. In addition, the smoking rate is considered to be high. Despite these conditions, few prevalence studies of COPD epidemiology and diagnose have been performed in Mongolia. The spirometric test is a widely used diagnose for COPD. Aims: Healthy and over the 40 aged adults were evaluated of Pulmonary function test in Ulaanbaatar. Methods: Healthy, over the 40 aged residences were admitted for this study from II sub-district, in Khan-Uul district of Ulaanbaatar city. In this cross-sectional study. Health information was collected 184 subjects between 01-03 July in 2013; spirometry device was named Hichest–105 Japan that was employed for this study. Studies were using the acceptability standards outlined, and data were compared with personal reference data generated on Asian subjects which were performed abnormally to evaluated by global initiative obstructive lung decreases (GOLD). Data were analyzed using SPSS 20 software. Results: A total of 134 subjects (age 52.9±9.8, man 32.8%) were performed PFT which were interpreted normal 73.9% (sum of man 65.0% and woman 79.4% ), abnormal 26.1% which were typed obstruction 17.2% (23), restriction 6% (8), mixed 3% (4). Airflow obstruction were determined in all man 25% (11), woman 13.3% (12) which were classified mild 43.4% (man 54.5%, woman 33.3%), moderate 52.2% (36.3% vs. 66.7%) and severe 4.3% man 1 GOLD degree. Undetermined a very severe obstruction. Normal PFT subjects were compared a group of gender and age group which man was significantly higher than the women (p<0.05). Age group of PFT decrease was no difference in gender (p>0.05) also no difference in BMI (p>0.05). Normal PFT subjects were compared with predicted values were used to Asian population which was significantly lower than FEV1 (0.15±0.36 l), PEF (1.92±1.31 l) and same deference occurred man (FEV1 0.19±0.42 l, PEF 2.04±1.64), women (0.14±0.33 l vs. 1.86±1.15 l). The decrease of FEV1 was defined in over the 60 age group higher than other age groups. Conclusion: Not only observed an air flow limitation prevalence dominance in all case but also COPD prevalence diagnosed man were higher than women. Normal PFT subjects were compared with predicted values were used to Asian population which was significant air flow limitation started early.

Keywords: PFT, obstruction, FEV1, COPD

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Authors: Nalan Kaya, Gonca Ozan, Elif Erdem, Neriman Colakoglu, Enver Ozan

Abstract:

The toxic effects of tobacco smoke exposure have been detected in numerous studies. Ellagic acid (EA), (2,3,7,8-tetrahydroxy [1]-benzopyranol [5,4,3-cde] benzopyran 5,10-dione), a natural phenolic lactone compound, is found in various plant species including pomegranate, grape, strawberries, blackberries and raspberries. Similar to the other effective antioxidants, EA can safely interact with the free radicals and reduces oxidative stress through the phenolic ring and hydroxyl components in its structure. The aim of the present study was to examine the protective effects of ellagic acid against oxidative damage on lung tissues of rats induced by tobacco smoke. Twenty-four male adult (8 weeks old) Spraque-Dawley rats were divided randomly into 4 equal groups: group I (Control), group II (Tobacco smoke), group III (Tobacco smoke + corn oil) and group IV (Tobacco smoke + ellagic acid). The rats in group II, III and IV, were exposed to tobacco smoke 1 hour twice a day for 12 weeks. In addition to tobacco smoke exposure, 12 mg/kg ellagic acid (dissolved in corn oil), was applied to the rats in group IV by oral gavage. Equal amount of corn oil used in solving ellagic acid was applied to the rats by oral gavage in group III. At the end of the experimental period, rats were decapitated. Lung tissues and blood samples were taken. The lung slides were stained by H&E and Masson’s Trichrome methods. Also, galactin-3 stain was applied. Biochemical analyzes were performed. Vascular congestion and inflammatory cell infiltration in pulmonary interstitium, thickness in interalveolar septum, cytoplasmic vacuolation in some macrophages and galactin-3 positive cells were observed in histological examination of tobacco smoke group. In addition to these findings, hemorrhage in pulmonary interstitium and bronchial lumen was detected in tobacco smoke + corn oil group. Reduced vascular congestion and hemorrhage in pulmoner interstitium and rarely thickness in interalveolar septum were shown in tobacco smoke + EA group. Compared to group-I, group-II GSH level was decreased and MDA level was increased significantly. Nevertheless group-IV GSH level was higher and MDA level was lower than group-II. The results indicate that ellagic acid could protect the lung tissue from the tobacco smoke harmful effects.

Keywords: ellagic acid, lung, rat, tobacco smoke

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